Chlamydia trachomatis is a human pathogen of worldwide importance. This obligate intracellular bacterium is responsible for ocular, respiratory, and sexually transmitted diseases, many of which result in significant sequelae including blindness, small airways disease, infertility and ectopic pregnancy. The host immune response to chlamydial infection is characterized as both protective and pathogenic1. While protective immune responses likely occur at mucosal sites of bacterial invasion, the extent of this response and those that lead to clinical pathology in humans remain ill defined. This is in part due to the difficulty in studying human populations and our inadequate understanding of the host-pathogen immune interactions.
To date, the major outer membrane protein (MOMP) of C. trachomatis is the organism's most antigenically diverse protein. Its interactions with the host mucosal immune system are far encompassing and include the elicitation of T cell help for the production of antibodies2,3 and neutralizing infection in vitro4. Reactivity to monoclonal antibodies (MAb) against MOMP B cell determinants form the basis for immunotyping chlamydial strains into serological variants, or serovars5. These serovars have been grouped into the following classes: B class (serovars B, Ba, D, Da, E, L1, L2, L2a); C class (serovars A, C, H, I, Ia, J, Ja, K, and L3); and Intermediate class (serovars F, G, and Ga). Through the cumulative efforts of a number of mapping studies, serovar-, serovar class-, subspecies-, and genus-specific epitopes and T cell determinants have been mapped to variable segments (VSs) and constant (C) regions of MOMP2,3,5-28.
Over the last decade, analyses of the genetic diversity of the MOMP gene, ompA, have identified genotypes with surface antigens immunologically distinct from the parent serovar29-33. Consequently, serotyping of C. trachomatis has been limited by the MAbs available for such typing, evidenced by the fact that only through the development of additional MAbs were later serovars identified. Moreover, as new serotypes of the organism emerge, currently available MAbs may fail to identify them. The use of epitope mapping to identify determinants of newly identified ompA genotypes is not feasible because this technique is laborious, time consuming, and expensive since numerous recombinant fusion proteins2,5,14,16,28 or overlapping synthetic peptides need to be generated and tested3,6,7,11,13,15,24,25,27,34. Employing this technique for more extensive studies of functional domains on MOMP, including additional B and T cell recognition sites and HLA restriction12,17-19 would be important but also limited by the same factors.
There is a need in the art for methods for predicting structural and functional characteristics of a protein based on a nucleotide sequence encoding the protein and/or the amino acid sequence. The present invention addresses this need.